Genomics and gene transcription kinetics in yeast

Abstract

As an adaptive response to new conditions, mRNA concentrations in eukaryotes are readjusted after any environmental change. Although mRNA concentrations can be modified by altering synthesis and/or degradation rates, the rapidity of the transition to a new concentration depends on the regulation of mRNA stability. There are several plausible transcriptional strategies following environmental change, reflecting different degrees of compromise between speed of response and cost of synthesis. The recent development of genomic techniques now enables researchers to determine simultaneously (either directly or indirectly) the transcription rates and mRNA half-lifes, together with mRNA concentrations, corresponding to all yeast genes. Such experiments could provide a new picture of the transcriptional response, by enabling us to characterize the kinetic strategies that are used by different genes under given environmental conditions. Gene expression changes in eukaryotesGene expression in eukaryotes is a complex process that involves numerous successive steps, from the binding of transcription factors to their target sequence to the posttranslational modification of proteins. After any environmental change (e.g. a temperature shift), the cell adapts to the new circumstances by, among other responses, altering the expression of certain genes. Each step of gene expression can be quantitatively regulated. However, it is not always recognized that the rate at which gene expression changes is as important as the magnitude of that change. 77Cells need to cope with the 'time factor' throughout the process of modification of gene expression. For example, the transcription and translation processes take place at a limited speed. RNA polymerase II has been calculated to travel at ~18-42 nucleotides per second on chromatin templates [1][2][3][4][5]. This speed might not be constant across all genes and conditions, but if we take it to be a representative average value, then the time required to 'read' a gene is not negligible: 25-50 seconds for 1 kb (the average length of a yeast gene [6]); 2-3 minutes for a typical mammalian gene [7]; and up to 16 hours for certain long intron-containing human genes [3]. Pausing and termination further delay the release of mRNA molecules from the genes (as discussed in Ref. [4]). Moreover, maturation and transport of the mRNA to the cytoplasm [4,8], and translation and transport of the protein to its correct subcellular location are also time-consuming processes. Therefore, the appearance of a 'functional protein' after a 'transcription order' has been received can take from several minutes in unicellular eukaryotes to several hours for long genes in vertebrates. This limits how fast a cell can react to environmental shifts. Furthermore, an optimal response requires an ordered sequence of gene expression changes. Therefore, the cell must control the timing of these changes in a gene-specific manner.Here, we focus on the transcription kinetics of the yeast Saccharomyces cerevisiae, highlighting ...

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